Diabetes Drugs Flashcards
Alpha cells
glucagon and proglucagon
Beta cells
insulin , C-peptide, proinsulin, amylin
Delta cells
somatostatin
Epsilon cells
Ghrelin
Insulin and glucagon are
physiological antagonist
Explain urination frequency and osmolarity in Diabetes Mellitus
There is increased glucose which means water retention, because water follows salt because the body is trying to dilute and get rid of high blood sugar.
Types of Diabetes Mellitus
T1
T2
Gestational
Other conditions of toxicity
Explain diabetic keto acidosis
There is low insulin in the body , which leads to high blood sugar. This leads to frequent urination, dehydration, and loss of electrolytes and hypovolemia. Counter regulatory hormones are released such as glucagon, cortisol, growth hormone and epinephrine, but there is still no insulin.
The body then starts breaking down triglycerides into FFA and glycerol. The glycerol will be used for gluconeogenesis, but it can’t be used because no insulin. The FFA will be metabolized to ketone bodies (B-hydroxybutyate) and also acetone. The ketone bodies will undergo metabolism via the Kreb’s cycle. This process can cause the blood to become acidic and is exacerbated by lower blood volume due to frequent urination causing fluid loss.
Insulin is first synthesized as
proinsulin and C-peptide which both have no physiological activity (Two AA chains connected by cysteine bridges)
How is insulin released?
Carbs influx the cell, the cells that synthesize insulin get more and more glucose which means more ATP. The increase in ATP results in the inhibition of voltage gated potassium channels. This causes depolarization of the cell membrane which leads to opening of voltage gated calcium channels to allow influx of calcium into the cells . This leads to degranulation and exocytosis of insulin.
What happens when insulin is released?
It binds to TK receptors which phosphorylates themselves. The phosphorylation leads to the increased number of glucose transporters in the cell membrane. IN Type 1 diabetes, this never happens.
Insulin is a storage hormone. Explain its effect on liver, muscles, and fat tissue.
Muscles: increases the synthesis of glucagon which is only for use by the muscles themselves, the glucagon can’t be used to raise glucose levels in the blood stream.
Liver: Increases glycogen synthesis in hepatocytes this is for use in fasting. The stores in the liver will be used to increase glucose levels in the blood stream.
Fat: Insulin will make adipocytes to stop lipolysis and store glucose. Early in the morning a high carb breakfast will stop lipolysis.
The body will give glucose to
the brain, muscles, and the excess to fat tissue
When exercising . explain importance of strength training
You lose fat with strength training because this directs glucose to muscles and less is directed to fat tissue. This prevents storage of too much fat.
When sugars in the body interact with proteins, this is like frying a steak. Explain this …
Glycosylated proteins leads to more AGEs (Advanced glycosylation end products) AGEs leads to more RAGEs which target tissues such as kidneys, heart, retina and can have damaging effects.
Aging effect on immune system
Decrease adaptive
Increase innate
Rapid acting insulin (pump)
Insulin lispro, insulin aspart, insulin glulisine
Short-Acting Insulin
“Actual insulin” phys ligand ..given in gestational diabetes
Intermediate-Acting and Long Acting Insulin
Insulin NPH; Insulin Glargine; Insulin Detemir
Mixtures of insulins
NPL, NPA
Before bed insulin
Glargine and Detemir
Complications associated with insulin
Hypoglycemia
Allergic reactions
Lipodystrophy
Increased cancer risk
Why does insulin cause weight gain?
Insulin is a storing hormone. It enhances fat storage and inhibits lipolysis.
What are secretagogues?
stimulates the release of patients on insulin( only used in type 2)
Secretagogues mechanism
target voltage gated potassium channels which leads to depol which leads to calcium influx and insulin degranulation
Old class of insulin secretagogues
Glimeperide Glyburide Glipizide Chlorpropamide Tolbutamide
Old class of secretagogues causes (sulfonyureas)
weight gain , hematologic toxicity, skin rashes (if patients react to drugs with sulfonyl groups for antibiotic purposes, then they will most certainly react to the old class secretagogues.
Newer gen secretogogues
Meglitinide analogues –these will cause weigh gain but no rash because no sulfonyl group. Repaglinide and nateglinide.
Biguanides (Metformin)
Activates AMP=Activated protein kinase (AMPK) this results in the reduction of hepatic glucose.
Pioglitazone
Targets PPAR-gamma which are TFs which control genes involved in Glucose and Fatty acid metabolism.
Increase glucose transporter expression, decreased free fatty acid level
Rosiglitazone
Targets PPAR-gamma which are TFs which control genes involved in Glucose and Fatty acid metabolism.
Increase glucose transporter expression, decreased free fatty acid level
Acarbose
Inhibitor of alpha Glucosidase Reducing Postmeal Glucose Level (Inhibits enzyme from breaking down complex carbs into simple sugars). Increase gas, etc due to build up of carbohydrates.
Exenatide
Agonist of Glucagon-Like Peptide (GLP-1) receptors and helps insulin do its job. GLP-1 is released in the gut.
GLP-1 is degraded by DPP-4 and if this DDP-4 is inhibited, then it will increase the activity of GLP-1 which results in insulin better doing its job.
Line of treatment for T2 DM
Diet and exercise
“ + metformin
metformin + another agent
metformin + two other agents
metformin + more complex insulin regimen+ other non-insulin agent.
